A. Our laboratory has been studying the molecular biological aspects of signals that trigger the malignant phenotype of human breast cancer cells. We have used the MCF-7 human breast cancer cell line as a model for hormone-dependent mammary tumorignesis. These cells require exogenous estradiol supplementation for maximal in vitro growth rate and in vivo tumorigenecity. Using DNA transfection we have introduced the v-ras-H oncogene into the MCF-7 cells and have shown that the expression of this activated gene results in the bypass of these cells' hormone dependence. We have followed up these studies by creating derivative cell lines with different c-ras-H mutants and are currently studying the phentotype of these different transfectants. A second oncogene which may play a role in human breast cancer is the erbB oncogene which codes for the EGF receptor protein. It appears that the expression of the c-erbB gene is inversely related to hormone dependence in many human breast cancer cell lines. We have constructed an MCF-7 derivative cell line transfected with the v-erbB gene to characterize a breast cancer cell with a constitutively activated EGF receptor and assess the effect of this on the hormone dependence and tumorigenesis potential of the cell.